Chen San-Chi, Ho Hsiang-Ling, Liu Chien-An, Hung Yi-Ping, Chiang Nai-Jung, Chen Ming-Huang, Chao Yee, Yang Muh-Hwa
Institute of Clinical Medicine, National Yang Ming Chiao Tung University, No. 201 Shipai Road, Sec. 2, Taipei, Taiwan.
School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
BMC Cancer. 2025 Feb 4;25(1):199. doi: 10.1186/s12885-025-13568-4.
Alpha-fetoprotein (AFP) is a key biomarker for hepatocellular carcinoma (HCC), but 30-40% of cases are AFP-negative. Prothrombin induced by vitamin K absence II (PIVKA-II) is more sensitive for HCC detection, though its role in systemic therapy remains underexplored. This study aimed to evaluate PIVKA-II in non-AFP-secreting HCC treated with systemic therapy.
Patients with unresectable HCC undergoing systemic therapy were enrolled. Baseline imaging and PIVKA-II levels were recorded. After 8-12 weeks of treatment, response was evaluated through imaging and repeat PIVKA-II measurements.
A total of 116 treatment assessments from 61 cases were analyzed. Baseline PIVKA-II levels correlated with tumor size, but not tumor number or liver function. PIVKA-II regression (≥ 50% reduction) and progression (≥ 50% increase) were defined using ROC analysis. Imaging showed 71.0% objective response in the regression group, 50.0% stable disease in the stable group, and 83.7% progressive disease in the progression group (p < 0.001). This association held for targeted therapies, immune checkpoint inhibitors, and chemotherapy. Progression-free survival (PFS) for the regression, stable, and progression groups was non-reached, 6.7, and 3.2 months (p = 0.0002), and overall survival (OS) was non-reached, non-reached, and 18.5 months (p = 0.02).
This study is the first to establish the "50-50 rule" for PIVKA-II response in non-AFP-secreting HCC treated with systemic therapy, highlighting its value as a surrogate marker for radiological outcomes and prognosis.
甲胎蛋白（AFP）是肝细胞癌（HCC）的关键生物标志物，但30%-40%的病例为AFP阴性。维生素K缺乏诱导蛋白II（PIVKA-II）对HCC检测更为敏感，不过其在全身治疗中的作用仍未得到充分探索。本研究旨在评估PIVKA-II在接受全身治疗的非AFP分泌型HCC中的作用。
纳入接受全身治疗的不可切除HCC患者。记录基线影像学检查结果和PIVKA-II水平。治疗8-12周后，通过影像学检查和重复测量PIVKA-II评估疗效。
共分析了61例患者的116次治疗评估结果。基线PIVKA-II水平与肿瘤大小相关，但与肿瘤数量或肝功能无关。使用ROC分析定义PIVKA-II下降（≥50%）和升高（≥50%）。影像学检查显示，下降组客观缓解率为71.0%，稳定组疾病稳定率为50.0%，升高组疾病进展率为83.7%（p<0.001）。这种关联在靶向治疗、免疫检查点抑制剂和化疗中均成立。下降组、稳定组和升高组的无进展生存期（PFS）分别为未达到、6.7个月和3.2个月（p=0.0002），总生存期（OS）分别为未达到、未达到和18.5个月（p=0.02）。
本研究首次为接受全身治疗的非AFP分泌型HCC建立了PIVKA-II反应的“50-50规则”，突出了其作为放射学结果和预后替代标志物的价值。
